The Pathogenic hypothesis of homosexuality, or the gay germ hypothesis, argues that a pathogenic cause of homosexuality is pointed to by the reduced number of offspring produced by homosexuality, meaning evolution would strongly select against it, by the low identical twin concordance for homosexuality, which further argues against genetic influence, and by analogue with diseases that alter brain structure and behavior, such as narcolepsy, which are suspected of being triggered by viral infection. It is inaccurate to refer to this hypothesis as a theory, as a theory represents a well-tested and verified hypothesis that has withstood all currently possibly scientific scrutiny and inquiry.

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Cochran points out that conditions which strongly affect the ability to reproduce fall into two categories - those that are very rare (affecting about 1 in 10,000 births or less), and those that result from genes which actually confer evolutionary advantage in certain situations, and disadvantage in others. (Such as sickle cell anemia.) Homosexuality is reportedly present in more than 1 in 100 people. Assuming it is not caused by a recent mutation, and that it does not fall into the selective advantage category, a reasonable explanation would be that it is caused by a germ or other environmental factor.

Cochran claims that theories of the cause of narcolepsy - that it is an auto-immune disease triggered by a virus - make the mechanism of selective brain modification plausible. He also claims that only humans and sheep exhibit homosexual behavior at population levels near 1% or greater. He says that given their physical proximity, it would be plausible to expect a pathogen that affected both species.

Other theories that propose mechanisms of selective advantage (thus not requiring a pathogenic explanation) do exist. Some studies also claim that sexual orientation has high but not 100% heritability (which would indicate that genes are important, though not absolute determiners). See Genetics and sexual orientation.

Many scientists, such as William Byne who is a brain researcher at the Mount Sinai School of Medicine in New York, suggest that "Cochran and Ewald are guilty of pathologizing homosexuality" (in the words of Crain, 1999). In contrast, Michael Bailey, professor of psychology at Northwestern University, asks, "Suppose we found that a form of genius was also caused by a virus. Would that mean that genius is a disease?" (Crain, 1999) Cochran and Ewald point out that some bacteria are more symbiotic in nature, such as certain species which aid digestion in mammals.

In social debates about the morality of homosexual acts and the legal regimes that should regulate or protect sexual behaviors or identities, different sides often make different judgments about whether or not atypical sexual orientations are "diseases," or "differences" (like race or eye color). (Some also believe that homosexuality is a choice, not an inherent condition.) Participants in the debate are thus concerned about empirical theories that may influence public opinion one way or the other.

Cochran asks, rhetorically, "Should we drop a theory that has a chance of being correct on the grounds that it might upset people?...The facts of the natural world don’t seem to care what we feel, and our feelings don’t always help in figuring out how things really work." (Crain, 1999)